Venous thromboembolism with raloxifene

Raloxifene is well tolerated overall. Hot flushes occur more frequently in women recently finishing menopause or discontinuing estrogen therapy (ET). Endometrial bleeding occurs rarely. Raloxifene is contraindicated in women with an active or past history of venous thromboembolism. Therapy should be stopped if a patient anticipates extended immobility. 

Shand et al. (2002) have shown that, compared with placebo-treated subjects, long-term raloxifene treatment in postmenopausal women, at a dose of either 60 or 120 mg/d, was not associated with adverse changes in hemorheological factors (determinants of blood viscosity) that may contribute to venous thromboembolism. 

Women who are lactating or who are or may become pregnant (see Warnings) women with active or a history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis hypersensitivity to raloxifene or other constituents of the drug. 

Treatment of postmenopausal women with osteoporosis with raloxifene (60mg/day or 120mg/day for 36 months) was found to significantly increase bone mineral density in the spine and femoral neck and decrease the risk of vertebral fracture compared to the placebo treatment.Treatment with raloxifene increased the risk of venous thromboembolism compared to the placebo group and was also associated with a lower risk of breast cancer and did not cause breast pain or vaginal bleeding. 

An extensive literature review has provided a useful assessment of the benefit to harm balance of raloxifene (20). The findings were reassuring. One large fracture prevention trial provided the best evidence that raloxifene 60 mg/day for 3 years reduced the relative risk of vertebral fractures by 30-50% in women with prevalent fractures or osteoporosis. The extraskeletal effects of raloxifene include a reduction in total cholesterol and low density lipoprotein cholesterol concentrations. Raloxifene was not associated with endometrial hyperplasia, and there was a 72% reduction in the incidence of invasive breast cancer. Adverse events associated with raloxifene included an increase in the absolute risk of venous thromboembolism and increased risks of hot... 

Finally, the RUTH study (Raloxifene Use for the Heart)38 was a placebo-controlled clinical trial following over 10,000 postmenopausal women with coronary heart disease (CHD) or with multiple risk factors for CHD.44 16 This trial demonstrated 44% reduced incidence of invasive breast cancer versus placebo, with 0.6% absolute risk reduction,47 thus confirming the findings from MORE and CORE, while also demonstrating that raloxifene did not increase or decrease risk for coronary events or stroke. However, there was an increase in stroke mortality and incidence of venous thromboembolic events (VTEs) as compared to placebo, already seen in MORE, which resulted in a recommendation that raloxifene should not be used for the prevention or reduction of the risk of cardiovascular disease.21... 

MORE" 7705 postmenopausal women with osteoporosis Raloxifene 60 or 120 mg/ day or placebo 76% lower risk of estrogen receptor-positive breast cancer after 4 years of raloxifene therapy Raloxifene can cause or exacerbate hot flushes. Also, it increases the risk of venous thromboembolism by about 2-fold. 

I Administration. Overall, raloxifene therapy is well tolerated, but hot flushes occasionally cause women to discontinue therapy (see Table 88-6). Raloxifene use is associated with a threefold increased risk of venous thromboembolism, similar to the increased risk seen in women taking estrogens. Raloxifene is contraindicated for those with active thromboembolic disease. Therapy should be stopped if a patient anticipates a signiflcant period (several hours or more) of immobility. Raloxifene does not induce endometrial bleeding. 

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